The emergence of technologies enabling isolation of adult stem cells has allowed evaluation of cell therapeutics for central nervous system disorders with a path for clinical development. Much promise has been shown using stem cells in acute disease models such as stroke or hypoxic injury to the brain, and as well to chronic degenerative diseases such as Parkinson's or spinal cord fracture. We will evaluate physiological benefit derived from treatment of injured animals receiving multi-potent progenitor cells (MPC) derived from bone marrow. We propose to extend pre-clinical efficacy data in a rat model neonatal hypoxic-ischemic injury. Our preliminary data supports a model in which administration of therapeutic cell populations soon after injury provides benefit through trophic influences regulating local inflammatory responses and vascular permeability, vasculogenesis, neurogenesis or recruitment of endogenous stem or progenitor cells. MPC can be isolated from animal and human bone marrow, and using both in vivo and in vitro models produce differentiated progeny of the CMS. Because these cells can be expanded to a large cell number, and do not readily stimulate an allogeneic immunological reaction when in a non-differentiated state, they are ideal candidates as an "off-the-shelf clinical product. In our Phase I proposal, we will test both interstitial injection and intra-arterial delivery of stem cells to animals subjected to hypoxic-ischemic injury. We will evaluate route of delivery showing most benefit and test for cell fate and long-term persistence, allowing transition to a Phase II pre-clinical disease model for safety and benefit testing in primates. It is our intention to commercialize a stem cell therapeutic product for acute ischemic injury to the brain. [unreadable] [unreadable] [unreadable]